EP1285256B1 - Verfahren zur analyse einer streuenden probe durch zeitaufgelöste messung - Google Patents

Verfahren zur analyse einer streuenden probe durch zeitaufgelöste messung Download PDF

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Publication number
EP1285256B1
EP1285256B1 EP01936568A EP01936568A EP1285256B1 EP 1285256 B1 EP1285256 B1 EP 1285256B1 EP 01936568 A EP01936568 A EP 01936568A EP 01936568 A EP01936568 A EP 01936568A EP 1285256 B1 EP1285256 B1 EP 1285256B1
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Prior art keywords
sample
predetermined delay
signal
signals
characteristic
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French (fr)
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EP1285256A1 (de
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Jean-Michel Tualle
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Universite Sorbonne Paris Nord Paris 13
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Universite Sorbonne Paris Nord Paris 13
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/4795—Scattering, i.e. diffuse reflection spatially resolved investigating of object in scattering medium
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters

Definitions

  • the present invention relates to a method for analyzing a scattering sample by time-resolved measurement of diffuse light in this sample.
  • Measurements can be made in reflectance or transmittance.
  • Reflectance measurements are used in particular to determine the rate of oxygenation of blood hemoglobin.
  • Measurements in transmittance are used in particular for the detection of cancerous tumors of the breast.
  • the images obtained by the time-resolved transmittance measurement of diffuse light produce very contrasting images allowing to detect a tumor clearly.
  • the spatial resolution of the images is relatively poor.
  • the source producing the light pulse is adapted to provide a very brief pulse.
  • the light source used is a titanium-sapphire laser. This one is very expensive.
  • the detection implemented is tricky.
  • the solution used in the device described in this document implements an avalanche photodiode connected to an electronic time gate in order to determine the number of photons transmitted during a determined period of time.
  • the avalanche photodiode has a relatively long response time which deteriorates the potential contrast of the time gate.
  • a source is commonly used to produce short pulses such as pulse lasers which are expensive.
  • the aim of the invention is to propose a device for analyzing a scattering sample by a time-resolved measurement of diffuse light, the cost of which is low.
  • It also relates to an equipment for measuring the content of a specific constituent in a part of a living organism comprising an installation for analyzing a scattering sample as described above, and means for calculating said content. in a constituent determined according to the result of the analysis provided by said installation.
  • said analysis facility is adapted to produce interference signals from backscattered light by an organ of a human being or an animal, and said calculating means are adapted to calculate the oxygenation rate of this organ.
  • said analysis facility is adapted to produce interference signals from diffuse light transmitted through an organ of a human being or an animal.
  • the installation represented on the figure 1 illustrates the principle of the analysis method according to the invention.
  • This facility allows the transmittance analysis of a scattering sample by time-resolved measurement of diffuse light. It uses an interferometric technique to carry out the measurement and comprises for this purpose an interferometer designated by the general reference 11.
  • the installation implements a temporally coherent and wavelength-modulated light source 14 so as to simulate, by appropriate processing of the detected interference signal, an incoherent source.
  • the source 14 comprises a laser cavity 16 connected to a control unit 18 able to provide the wavelength modulation of the beam produced by the laser cavity 16.
  • the laser cavity 16 is for example a laser diode or an extended cavity laser diode. It is adapted to produce a temporally coherent monochromatic light beam.
  • the central wavelength of emission is chosen according to the applications. According to a particular mode of implementation of the method, several different central wavelengths are successively implemented, thus making it possible to perform spectroscopic measurements. They are for example equal to 780 nm and 850 nm for the analysis of tissue oxygenation rate.
  • the control unit 18 whose practical realization is within the reach of the skilled person, is adapted for periodic modulation of the wavelength of the beam produced by the diode 16.
  • This modulation is advantageously a sinusoidal modulation.
  • the amplitude ⁇ of this modulation is of the order of a few hundredths of a nanometer.
  • the modulation of the light produced by the diode 16 is carried out continuously, avoiding mode jumps.
  • the modulation frequency f is chosen sufficiently fast so that the scattering medium can be regarded as immobile during the modulation period f -1 .
  • the modulation frequency is advantageously between 0.1 and 10 kHz and is for example chosen equal to 1 kHz.
  • a lens 20 ensuring the adjustment of the width of the incident beam produced by the diode.
  • the incident beam denoted 22 is sent to the interferometer 11 which comprises, at the input, a semi-reflecting mirror 23 ensuring the separation of the incident beam 22 in two beams 24 and 26. These two beams 24, 26 propagate respectively following a reference arm 24A of the interferometer and following another arm 26A containing the sample.
  • the beam 26 is first sent into an optical system known per se to adjust the difference in operation between the optical paths of the two arms of the interferometer.
  • the beam 26 is sent by a mirror 30 to the sample 10 forming the diffusing medium.
  • a lens 32 may advantageously ensure the focusing of the beam at a given point of the sample.
  • Means 34 for collecting the scattered beam such as a converging lens collect the beam at the output of the sample 10.
  • the scattered light is then sent by a mirror 36 to a semi-reflecting mirror 38 ensuring the superposition of the scattered beam and the beam 24 propagating along the reference arm of the interferometer.
  • the interferometer 11 comprises means allowing the position of the beam 26 arriving on the sample 10 to be modified slightly continuously.
  • the modification of the position of the beam is made during the analysis, in order to increase the accuracy of the this, as will be explained later.
  • These means comprise, for example, members for moving the mirror 30 and / or the convergent lens 32, in order to modify the position of the beam on the sample and / or the angle of incidence of the beam with respect to the sample.
  • the interferometer advantageously comprises, downstream of the sample 10 in the arm 26A, means for modifying the sample collection area diffuse light.
  • means for modifying the sample collection area diffuse light comprise, for example, members for moving the collection means 34 or the mirror 36.
  • the beam noted 40 obtained by superposition, at the output of the interferometer 11, is sent to means 42 for detection and analysis.
  • These means 42 comprise a detector 44 connected to an information processing unit 46 whose main means are described with respect to the figure 2 .
  • the detector 44 is for example a photodiode.
  • the characteristics of the optical systems placed in the arm 26A of the interferometer, downstream of the sample 10, are chosen so that the coherence surface of the beam diffused at the detector 44 is of the same order of magnitude as the active surface of this detector.
  • the information processing unit 46 is formed of a set of analog electronic circuits adapted to perform the functions described with reference to FIG. figure 2 .
  • the unit 46 comprises a high-pass filter 50 for filtering the signal collected by the detector 44.
  • the cutoff frequency of the filter 50 is of the order of one to ten times the frequency f of modulation of the light emitted by the diode 16. In this case, the cutoff frequency is of the order of one kilo hertz.
  • the main purpose of the high-pass filter 50 is to suppress the DC component of the signal. It also ensures the elimination of low-frequency noise as well as possible parasitic effects related to wavelength modulation of diode 16.
  • the interference signal obtained at the output of filter 50 has a frequency much higher than the modulation frequency.
  • the signal obtained at the output of the filter is advantageously amplified by an optional amplifier 51.
  • the filter 50 is advantageously used, it can be omitted.
  • a multiplication stage 52 is provided at the output of the amplifier 51. It multiplies the filtered signal by a reference signal Ref (t, ⁇ 0 ).
  • the signal Ref (t, ⁇ 0 ) comes from a device 54 for producing this signal.
  • This device is for example a programmable signal generator or an analog electronic circuit consisting of a set of oscillators whose characteristic parameters can be adjusted.
  • the output of the multiplication stage 52 is connected to a stage 56 for extracting the DC component of the signal, that is to say for calculating its average value.
  • the signal Ref (t, ⁇ 0 ) is such that the DC component of the product of the reference signal Ref (t, ⁇ 0 ) and the signal measured by the detector 44, in the absence of a scattering medium in the second arm 26A of the interferometer is essentially zero, except if the delay ⁇ t between the two arms of the interferometer is approximately equal to ⁇ 0 , with ⁇ t near, ⁇ t being the temporal resolution.
  • the delay ⁇ t corresponds to the difference in optical path length between the two arms of the interferometer 11 in the absence of scattering sample, divided by the speed of light.
  • the combination of the interference signal and the reference signal Ref (t, ⁇ 0 ) acts as a time gate centered on the delay ⁇ 0 , this gate selecting the component of the interference signal corresponding to a delay ⁇ 0 with respect to time. of travel of the reference arm 24A of the interferometer.
  • the signal Ref (t, ⁇ 0 ) is produced using an optical interferometer devoid of sample and having a delay ⁇ 0 between the two arms, by filtering the DC component of the signal detected at the output of the interferometer and multiplying the result by another function generated by an analog electronic device, this function being canceled at the extremes of the modulation ⁇ (t).
  • This other function will be for example sin n (2 ⁇ ft).
  • the extraction by the stage 56 of the DC component of the product calculated by the stage 52 is obtained for example by implementing a low-pass filter.
  • the extracted signal is a continuous signal whose evolution is a slow evolution linked to the movements of the sample 10 or to the movements of the optical systems 30, 32 and / or 34, 36.
  • the extraction of the DC component is provided by an integrating device which integrates the signal obtained at the output of the stage 52 for exactly an integer of half-periods f -1 / 2 .
  • the signal from the stage 56 is sampled after each integration of this type.
  • the information processing unit further comprises a stage 58 for applying a non-linear function to the DC component of the signal obtained at the end of stage 58.
  • This function is, for example, an elevation at square, or any other even power, or the application of the absolute value function.
  • the result of the application of the temporal gate implemented during the multiplication carried out by the stages 52 to 58 is illustrated on the Figures 3 and 4 .
  • the signal represented in these figures is the DC component obtained at the output of the stage 58, as a function of the value of the predetermined delay ⁇ 0 .
  • the signal represented on the figure 3 is obtained from the installation of the figure 1 in which no sample is disposed in the arm 26A.
  • the peak of the peak corresponds to a delay substantially equal to 2080 ps, this value corresponding to the delay ⁇ t between the two arms of the interferometer.
  • the signal represented on the figure 4 is obtained, at the output of the stage 56, in the presence of a diffusing medium disposed in the branch 26A of the interferometer.
  • This figure also shows a first signal close to the origin of the times, this signal corresponding only to the diffuse light coming from the arm 26A, independently of the interference with the reference coming from the arm 24A. This signal is not used for the implementation of the method.
  • the next stage noted 60 of the unit 46 is adapted to average the signals obtained at the output of the stage 58 for a period of time. determined.
  • the average calculated by stage 60 is determined over a duration of the order of one second.
  • the stage 60 comprises for example a low-pass filter.
  • the calculation of the average is replaced by a simple summation of the sampled signals from the stage 58 or any other form of linear combination performed on these signals.
  • the signal obtained at the end of the stage 60 for a given value of the predetermined delay ⁇ 0 is proportional to the part of the diffuse energy which has a delay ⁇ 0 with respect to the travel time of the reference arm 24A of the interferometer, at ⁇ t near.
  • FIG 5 is represented an example of the signal obtained at the output of the stage 60, as a function of the predetermined delay ⁇ 0 .
  • This figure clearly shows a signal for values of the predetermined delay ⁇ 0 greater than the delay ⁇ t between the two arms of the interferometer.
  • the profile of the curve of the figure 5 has a net profile representative of the structure of the diffusing medium.
  • the delay ⁇ 0 makes it possible to determine the time required for the beam to pass through the sample, for example, by simply subtracting from the delay ⁇ 0 the delay time ⁇ t between the two arms of the interferometer, and adding a correction related to the thickness of the sample.
  • the signal of the figure 5 is represented on a larger scale on the figure 6 , where the origin of the times has been corrected for the delay ⁇ t between the two arms of the interferometer.
  • the evolution of the calculated average value is linked to a transformation of the relevant parameters in the medium studied.
  • the installation comprises several information processing units 46, each associated with a delay value ⁇ 0 , thus making it possible to obtain measurements of the diffuse energy for different delays ⁇ 0 .
  • the information processing unit 46 consists of an analog electronic device. However, alternatively, this information processing unit comprises an analog high-pass filter 50 at the output of which is provided an analog / digital converter. The set of treatments performed by stages 52 to 60 is then performed completely digitally by implementing an algorithm adapted in a computer. In this case, the different number of values ⁇ 0 for which the calculation is performed can be very large.
  • the signal obtained at the output of the stage 58 fluctuates on the same time scale as the signal obtained at the output of the stage 56. These fluctuations are due to the movements in the scattering medium itself when this medium is a biological environment. These movements induce fluctuations on timescales of the order of a millisecond.
  • the setting in motion is controlled so that the time scale of the time fluctuations is greater than the modulation period f -1 .
  • the frequency of displacement of the beam is less than that of the wavelength modulation of the incident light.
  • An observation installation employing an interferometer, and means for transmitting a temporally coherent light beam and modulated in wavelength, as well as processing means as described above, can advantageously be implemented for the reflectance measurement of the oxygenation rate of the hemoglobin of a human being.
  • the equipment for measuring the oxygenation rate illustrated on the figure 7 comprises a first laser diode 100 and a second laser diode 102 whose central emission wavelengths are respectively ⁇ 1 and ⁇ 2. These two diodes are each controlled by a control unit 104 and 106 for modulating the wavelength of the light emitted, as described in the previous embodiment.
  • An automatic shutter 108 is disposed at the output of the laser diodes 100 and 102 so as to selectively illuminate an interferometer denoted 109 with one or the other of the light beams emitted by these diodes.
  • the output of the automatic shutter 108 is coupled to an optical fiber 110 by suitable coupling means 111.
  • the fiber 110 is a monomode optical fiber.
  • the fiber 110 conveys the light to a coupler 50/50 denoted 112 for separating the incident light and directing it along the two arms denoted 114 and 116 of the interferometer.
  • the reference arm 114 is formed by a monomode optical fiber 118.
  • the second arm 116 comprises a monomode optical fiber 120 forming an emitting fiber for bringing the incident beam to the sample to be studied.
  • the end of the optical fiber is placed on the arm of a patient.
  • the second arm 116 of the interferometer Downstream of the sample to be studied, the second arm 116 of the interferometer comprises a second optical fiber, denoted 122, monomode constituting an optical fiber for collecting diffuse light. Its free end is placed near the free end of the emitting fiber 120 to collect backscattered diffused light.
  • the optical fibers 118 and 122 are connected to each other by a 50/50 coupler, denoted 124, allowing the superposition of the transmitted light beams in the two arms of the interferometer.
  • coupler 124 The output of coupler 124 is connected to detection and analysis means 126 similar to means 42 of the embodiment of FIG. figure 1 .
  • an optional vibrator 130 is applied to the emitting optical fiber 120, and / or the receiving fiber 122, in order to cause a slight displacement thereof during the analysis to cause fluctuations in the signal and thus to improve, as explained above, the accuracy of the measurement performed.
  • the scattered light is measured for different delays ⁇ 0 , as described with respect to the embodiment of the figure 1 .
  • the equipment comprises, connected to the detection and analysis means 126, a unit 132 for calculating the rate of oxygenation of hemoglobin.
  • the oxygenation rate of the hemoglobin is deduced from the medium absorption coefficients calculated at the two wavelengths ⁇ 1, ⁇ 2 specific to the diodes 100 and 102.
  • the calculation of the absorption coefficient is made, according to a relationship known per se, from the exponential decay of light scattering as a function of time, this decay being defined from the different measurements made at different delays ⁇ 0 .
  • the installation illustrated on the figures 1 and 7 only allow for a time-resolved measurement at a particular point in the sample
  • the installation illustrated on the figure 8 is an imaging equipment that makes it possible to create a two-dimensional image of the studied sample.
  • This equipment has a structure substantially similar to that of the installation of the figure 1 .
  • elements identical or similar to those of this embodiment are designated by the same reference numbers.
  • the arm 26A of the interferometer in which the sample is placed comprises, upstream of the sample, a telescope 150 allowing the widening of the beam 26 propagating according to of arms. Thus, most of the surface of the sample is illuminated by the incident beam.
  • the reference arm 24A of the interferometer has a telescope 152 also enlarging the diameter of the beam 24 propagating along this arm.
  • the point sensor 44 used in the embodiment is here replaced by a network of sensors or independent pixels 154.
  • This network comprises a set of sensors distributed in line and in column.
  • Each detection sensor is associated with an integrated circuit that forms the high-pass filter 50 and amplifies the signal.
  • the signal from each sensor thus filtered and amplified is then multiplied by the reference signal Ref (t, ⁇ 0 ) and then integrated over an integer of half-periods to extract the DC component.
  • the steps of calculating a nonlinear function and the average of the results of this function are preferably performed numerically for each sensor.
  • the set of results obtained for each sensor is sent to a unit 156 adapted to produce an image of the sample studied as a function of the results received.
  • the value of the delay ⁇ 0 is advantageously adjusted so as to obtain a contrasting image by selecting the diffuse light at short times.
  • the telescope 150 and the collector system 34, 36 are associated with means making it possible to modify their inclination with respect to a reference axis in order to obtain transmittance images in different directions and thus allow a three-dimensional reconstitution of the medium from images obtained from the sample for different positions of the telescope 152 and the collector system 34, 36.
  • the equipment of the figure 8 is intended in particular for transmittance observation of an organ of a human being or animal. It is useful especially for the research of cancerous tumors of the breast.
  • the light source used may be formed of a simple laser diode.
  • the detection and analysis means can be made at a lower cost.
  • the electromagnetic fields are much less intense than pulsed, as is the case in the state of the art.
  • FIG 9 is illustrated a variant of the analysis method according to the invention for obtaining a time-resolved measurement of a quantity relative to diffuse light in the sample to be analyzed.
  • This variant differs from the process described with regard to Figures 1 to 6 only by the structure of the information processing unit 46 at its stages 56 and 58.
  • the output of the multiplication stage 52 is connected to a stage 56 'of extraction of the respective continuous components of the signals obtained at the output of the stage 52 for a determined duration, substantially equal to that used for the calculation of the calculated average by the stage 60 in the process described with regard to the figure 2 .
  • the continuous components thus obtained at stage 56 ' are denoted S i , where i denotes the i th signal at the output of stage 52 for the aforementioned duration.
  • the means used to obtain each continuous component S i are similar to those explained above.
  • non-linear is considered here in a broad sense, that is to say, in the case of functions with several variables, only the linear functions are excluded with respect to their variables taken together under vector form, such as the "sum of two vectors" function.
  • This nonlinear function is, for example, a product function applied to two distinct values S l .
  • the function g (S i , S i + ⁇ ) S i x S i + ⁇ where ⁇ is a non-zero positive integer.
  • Such a function is adapted to study the evolution of the value S i + ⁇ with respect to the value S i .
  • a biological medium is the seat of many movements and, despite the precautions of use including choosing a modulation frequency of the laser source 14 sufficiently high to consider the scattering medium 10 as immobile during the modulation period, the signal S i + 1 recorded following a signal S i is slightly different from this signal S i .
  • the signal S i + 2 is more so. More generally, there is a decorrelation of the signals S i + ⁇ and S i for ⁇ ⁇ 1. The evolution of this decorrelation as a function of ⁇ and ⁇ 0 is able to provide useful data on the nature and the intensity. movements in the analyzed environment 10.
  • the output of the stage 58 ' is connected to the average stage 60 of the signals obtained at the output of the stage 58', which average is a function, on the one hand, of the delay ⁇ 0 as previously, and on the other hand the value of the integer ⁇ .
  • One way of studying the decorrelation of the signals S i between them is to follow the evolution of this average resulting from the stage 60, for ⁇ increasing and ⁇ 0 set for example.
  • the data relating to the decorrelation of the signals S i provide information on the blood circulation in tissues such as the capillaries of the muscle, in addition to the measurement of the oxygenation rate as explained with regard to the figure 7 .
  • the time-resolved acquisition of this data makes it possible, for example, to isolate the contribution of the blood circulation in such capillaries compared to that in larger blood vessels.
  • the data relating to the decorrelation of the signals S i provide information on the state of vascularization of a tumor observed by the equipment of the figure 8 .
  • such tumors are over-vascularized.
  • the image contrast of the sample studied can be improved by using this decorrelation data.
  • FIG 10 is illustrated a second variant of the analysis method according to the invention wherein the means for combining the interference signal with the reference Ref (t, ⁇ 0 ) are constituted by amplitude modulation means of the laser source 16. More precisely, this variant of figure 10 differs from the embodiment described with regard to the Figures 1 and 2 only by what follows.
  • control unit 18 is replaced by a control unit 18 'adapted both to wavelength modulate the beam produced by the laser cavity, substantially analogously to the unit 18 of the figure 1 , and for amplitude modulating this laser beam, independently, from an amplitude modulation external signal.
  • a control unit 18 ' is within the reach of those skilled in the art, for example in the case of the use of a laser diode 16 mounted in extended cavity.
  • this additional amplitude modulation is capable of introducing into the analysis installation the reference signal Ref (t, ⁇ 0 ).
  • a device 54 'for producing a signal Ref (t, ⁇ 0 ) + Ref (T, 0) is provided, which is substantially similar in nature to the device 54 of FIG. figure 2 .
  • This device 54 ' is connected to the control unit 18' to provide the amplitude modulation external signal.
  • the recorded interference signal is then directly in the form of a combination, in particular of a product, comprising on the one hand a first term of a similar nature to the one from floors 50 and 51 of the figure 1 , that is to say a first term carrying the wavelength modulated information, and secondly a second term similar in nature to that from the device 54 of the figure 1 , that is to say a second term carrying the delay ⁇ 0 .
  • the combined signal thus obtained is characteristic of the delay ⁇ 0 .
  • This stage 60 'therefore only achieves a linear combination of the results from stage 58.
  • This variant makes it possible to simplify the processing unit 56 of the interference signals.
  • this variant makes it possible to simplify the array of sensors 154, each sensor being associated with an integrated circuit which filters, amplifies and extracts the DC component, with a half-period acquisition, of each interference signal. It is then possible to use a CCD camera as a means 156 to produce an image of the sample under study.
  • Another variant, not shown, of the analysis method according to the invention consists in combining together the two variants of the Figures 9 and 10 and in particular in the variant of the figure 10 to replace steps 56, 58 with steps 56 ', 58'.
  • the superposition mirror 38 can produce two beams 40, each of these two beams being detected by a respective sensor 44.
  • the difference obtained between these two detected beams gives information similar to that previously obtained from the single sensor, but advantageously less noisy.

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Claims (13)

  1. Verfahren zur Analyse einer lichtstreuenden Probe durch zeitaufgelöste Messung des Lichts, das in dieser Probe gestreut wird, das die folgenden Schritte umfasst:
    a) Beleuchten der Probe mit einem temporal kohärent und wellenlängenmoduliert einfallenden Lichtstrahl;
    b) Produzieren einer Reihe von Interferenzsignalen, die über ein Zeitintervall aufgezeichnet werden, durch die Überlagerung des Streulichts, das am Ausgang der Probe erhalten wird, und dem Licht, das am einfallenden Strahl, der die Probe beleuchtet, aufgenommen wird;
    c) Kombinieren jedes Interferenzsignals mit einem Referenzsignal, Ref(t,τ0), was ein Zeitgatter, gemittelt auf einer vorbestimmten Verzögerung τ0 erzeugt, um ein Signal zu produzieren, das für die vorbestimmte Verzögerung τ0 kennzeichnend ist;
    d) Extrahieren des Gleichstromanteils jedes Signals, der für die vorbestimmte Verzögerung τ0 kennzeichnend ist;
    e) Anwenden einer nichtlinearen Funktion auf jeden der Gleichstromanteile der Signale, die für die vorbestimmte Verzögerung τ0 kennzeichnend sind; und
    f) Ausführen einer linearen Kombination jedes der Bilder, nach dem Anwenden der nichtlinearen Funktion, der Gleichstromanteile der Signale, die für die vorbestimmte Verzögerung τ0 kennzeichnend sind.
  2. Verfahren nach Anspruch 1, wobei die nichtlineare Funktion eine Funktion ist, ausgewählt aus der Gruppe bestehend aus der Quadratfunktion und der Absolutwertfunktion.
  3. Verfahren nach Anspruch 1, wobei die nichtlineare Funktion eine Funktion mit mindestens zwei Variablen ist, die aus den Gleichstromanteilen der Signale gewählt sind, die für die vorbestimmte Verzögerung τ0 kennzeichnend sind, die aus der Reihe der Interferenzsignale erhalten werden, die über das Zeitintervall aufgezeichnet werden.
  4. Verfahren nach einem der vorhergehenden Ansprüche, worin für die Kombination jedes Interferenzsignals mit dem Referenzsignal Ref(t,τ0), der einfallende Strahl zusätzlich mittels einer Amplitudenmodulation amplitudenmoduliert ist, die die vorbestimmte Verzögerung τ0 einführt.
  5. Verfahren nach Anspruch 4, worin für eine Amplitudenmodulation, die gleich der Summe des Referenzsignals Ref(t,τ0) und eines Referenzsignals mit Verzögerung Null Ref(t,τ0) ist, die lineare Kombination eine Berechnung umfasst, bei der jedes der Bilder nach Anwendung der nichtlinearen Funktion der Gleichstromanteile der Signale, die für eine Verzögerung Null kennzeichnend sind, subtrahiert wird.
  6. Verfahren nach einem der vorhergehenden Ansprüche, wobei die lineare Kombination eine Berechnung des Mittelwerts jedes der Bilder nach Anwendung der nichtlinearen Funktion der Gleichstromanteile der Signale, die für die vorbestimmte Verzögerung τ0 kennzeichnend sind, umfasst.
  7. Verfahren nach einem der vorhergehenden Ansprüche, worin, während der Produktion der Reihe von Interferenzsignalen, eine relative Verschiebung zwischen dem einfallenden Strahl und der lichtstreuenden Probe erzwungen wird, wobei die Frequenz der erzwungenen Verschiebung kleiner ist als die Frequenz der Wellenlängenmodulation des Lichts des einstrahlenden Strahls.
  8. Verfahren nach einem der vorhergehenden Ansprüche, wobei das Referenzsignal Ref(t,τ0) eine Sinusfunktion des Produkts der vorbestimmten Verzögerung τ0, auf dem das Zeitgatter gemittelt ist, und der Wellenlängenmodulationsfunktion des einfallenden Strahls umfasst.
  9. Vorrichtung zur Analyse einer lichtstreuenden Probe durch zeitaufgelöste Messung des Lichts, das in dieser Probe gestreut wird, die umfasst:
    a) Mittel (16, 18; 100, 104, 102, 106) zum Beleuchten der Probe mit einem temporal kohärent und wellenlängenmoduliert einfallenden Lichtstrahl;
    b) ein Interferometer (11; 109) zum Produzieren einer Reihe von Interferenzsignalen, die über ein Zeitintervall aufgezeichnet werden, durch die Überlagerung des Streulichts, das am Ausgang der Probe erhalten wird, und dem Licht, das am einfallenden Strahl, der die Probe beleuchtet, aufgenommen wird;
    c) Mittel (52, 54) zum Kombinieren jedes Interferenzsignals mit einem Referenzsignal, Ref(t,τ0), was ein Zeitgatter, gemittelt auf einer vorbestimmten Verzögerung τ0, erzeugt, um ein Signal zu produzieren, das für die vorbestimmte Verzögerung τ0 kennzeichnend ist;
    d) Mittel (56) zum Extrahieren des Gleichstromanteils jedes Signals, der für die vorbestimmte Verzögerung τ0 kennzeichnend ist;
    e) Mittel (58) zum Anwenden einer nichtlinearen Funktion auf jeden der Gleichstromanteile der Signale, die für die vorbestimmte Verzögerung τ0 kennzeichnend sind; und
    f) Mittel (60) zum Ausführen einer linearen Kombination jedes der Bilder nach dem Anwenden der nichtlinearen Funktion der Gleichstromanteile der Signale, die für die vorbestimmte Verzögerung τ0 kennzeichnend sind.
  10. Einrichtung zum Messen des Gehalts an einem bestimmten Bestandteil in einem Teil eines lebenden Organismus, die eine Vorrichtung zur Analyse einer lichtstreuenden Probe nach Anspruch 9, und Mittel (132) zur Berechnung des Gehalts an einem bestimmten Bestandteil in Abhängigkeit vom Ergebnis der Analyse, die von der Vorrichtung bereitgestellt wird, umfasst.
  11. Einrichtung nach Anspruch 10, wobei die Vorrichtung zur Analyse angepasst ist, Interferenzsignale zu produzieren, die von dem durch ein Organ eines Menschen oder eines Tiers rückgestreuten Lichts ausgehen, und dadurch, dass die Mittel zur Berechnung angepasst sind, um die Oxygenierungsrate dieses Organs zu berechnen.
  12. Bildgebende Einrichtung, die umfasst:
    - eine Vorrichtung zur Analyse nach Anspruch 9, wobei die Vorrichtung angepasst ist, mehrere Reihen von Interferenzsignalen zu produzieren und zu behandeln, die aus dem Streulicht in mehreren benachbarten Regionen der Probe erhalten wurden, und so ein Analyseergebnis für jede der benachbarten Regionen der Probe bereitzustellen; und
    - Mittel (156), um ein Bild der Probe aus dem Analyseergebnis zu produzieren, das für jede der benachbarten Regionen der Probe bereitgestellt wird.
  13. Einrichtung nach Anspruch 12, wobei die Vorrichtung zur Analyse angepasst ist, um Interferenzsignale aus dem Streulicht zu produzieren, das durch ein Organ eines Menschen oder eines Tieres transmittiert wird.
EP01936568A 2000-05-18 2001-05-17 Verfahren zur analyse einer streuenden probe durch zeitaufgelöste messung Expired - Lifetime EP1285256B1 (de)

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FR0006392A FR2809180B1 (fr) 2000-05-18 2000-05-18 Procede d'analyse d'un echantillon diffusant par mesure resolue en temps
PCT/FR2001/001520 WO2001088507A1 (fr) 2000-05-18 2001-05-17 Procede d'analyse d'un echantillon diffusant par mesure resolue en temps

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US7356365B2 (en) * 2003-07-09 2008-04-08 Glucolight Corporation Method and apparatus for tissue oximetry
US7962198B2 (en) * 2005-04-27 2011-06-14 The Trustees Of Dartmouth College System and method for spectral-encoded high-rate hemodynamic tomography
US7811280B2 (en) * 2006-01-26 2010-10-12 Amo Manufacturing Usa, Llc. System and method for laser ablation calibration
FR2958430A1 (fr) 2010-04-02 2011-10-07 Univ Paris 13 Circuit electronique analogique de traitement d'un signal lumineux, systeme et procede de traitement correspondants
FR2992728B1 (fr) 2012-06-28 2015-03-06 Univ Paris 13 Procede d'analyse d'un echantillon diffusant par mesure resolue en temps et dispositif associe

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ES2310181T3 (es) 2009-01-01
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US6903825B2 (en) 2005-06-07
ATE400804T1 (de) 2008-07-15
EP1285256A1 (de) 2003-02-26
WO2001088507A1 (fr) 2001-11-22
FR2809180A1 (fr) 2001-11-23
DE60134738D1 (de) 2008-08-21
AU2001262449A1 (en) 2001-11-26

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